GNB4

G protein subunit beta 4, the group of G protein subunits beta|WD repeat domain containing

Basic information

Region (hg38): 3:179396087-179451476

Links

ENSG00000114450 ∙ NCBI:59345 ∙ OMIM:610863 ∙ HGNC:20731 ∙ Uniprot:Q9HAV0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Charcot-Marie-Tooth disease dominant intermediate F (Strong), mode of inheritance: AD
• Charcot-Marie-Tooth disease dominant intermediate F (Supportive), mode of inheritance: AD
• Charcot-Marie-Tooth disease (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Charcot-Marie-Tooth disease, dominant intermediate F	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	20627571; 23434117

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GNB4 gene.

• Charcot-Marie-Tooth disease dominant intermediate F (181 variants)
• not provided (53 variants)
• Inborn genetic diseases (33 variants)
• not specified (2 variants)
• Polyneuropathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GNB4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	36	3	42
missense	1	4	73	8		86
nonsense			5			5
start loss						0
frameshift			2			2
inframe indel			1			1
splice donor/acceptor (+/-2bp)			4			4
splice region			9	6	4	19
non coding			2	38	22	62
Total	1	4	90	82	25

Variants in GNB4

This is a list of pathogenic ClinVar variants found in the GNB4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-179401210-C-T		not specified	Benign (Jul 15, 2018)
3-179401216-A-G		Charcot-Marie-Tooth disease dominant intermediate F	Likely benign (Jul 01, 2022)
3-179401255-C-T		Charcot-Marie-Tooth disease dominant intermediate F	Likely benign (Jul 07, 2023)
3-179401278-C-A		Charcot-Marie-Tooth disease dominant intermediate F	Uncertain significance (Jan 19, 2022)
3-179401278-C-T		Charcot-Marie-Tooth disease dominant intermediate F	Benign/Likely benign (Apr 01, 2024)
3-179401279-A-C		Charcot-Marie-Tooth disease dominant intermediate F	Likely benign (Jul 14, 2023)
3-179401284-A-G		Charcot-Marie-Tooth disease dominant intermediate F	Likely benign (Mar 15, 2020)
3-179401295-C-T		Charcot-Marie-Tooth disease dominant intermediate F • Inborn genetic diseases	Uncertain significance (May 15, 2023)
3-179401295-CGG-C		Charcot-Marie-Tooth disease dominant intermediate F	Uncertain significance (Dec 26, 2018)
3-179401309-A-T		Charcot-Marie-Tooth disease dominant intermediate F	Uncertain significance (Aug 25, 2019)
3-179401313-A-G		Charcot-Marie-Tooth disease dominant intermediate F	Uncertain significance (Jul 10, 2023)
3-179401315-G-A		Charcot-Marie-Tooth disease dominant intermediate F	Likely benign (Jul 29, 2022)
3-179401317-C-A		Charcot-Marie-Tooth disease dominant intermediate F	Uncertain significance (May 12, 2022)
3-179401318-A-C		Charcot-Marie-Tooth disease dominant intermediate F	Likely benign (Jul 19, 2023)
3-179401322-GA-G		Charcot-Marie-Tooth disease dominant intermediate F	Benign (Oct 13, 2022)
3-179401322-G-GA		Charcot-Marie-Tooth disease dominant intermediate F • Inborn genetic diseases • GNB4-related disorder	Benign/Likely benign (Sep 01, 2023)
3-179401324-A-G		Charcot-Marie-Tooth disease dominant intermediate F	Uncertain significance (Oct 14, 2022)
3-179401325-AAAAAAATTCAGTAAAAAATTGGCAATTGTAGGGTTTTAGAATT-A		Charcot-Marie-Tooth disease dominant intermediate F	Likely benign (Apr 13, 2021)
3-179401329-A-G		Charcot-Marie-Tooth disease dominant intermediate F	Likely benign (Mar 28, 2018)
3-179401334-C-A		Charcot-Marie-Tooth disease dominant intermediate F	Likely benign (Aug 24, 2021)
3-179401334-C-G		Charcot-Marie-Tooth disease dominant intermediate F	Likely benign (Jan 11, 2022)
3-179401338-A-G		Charcot-Marie-Tooth disease dominant intermediate F	Likely benign (May 17, 2023)
3-179401339-A-G		Charcot-Marie-Tooth disease dominant intermediate F	Likely benign (Jul 06, 2023)
3-179401348-C-T			Likely benign (Apr 12, 2019)
3-179401445-AAAT-A			Benign (Aug 10, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GNB4	protein_coding	protein_coding	ENST00000232564	9	52389

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00237	0.995	125732	0	16	125748	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.11	112	195	0.575	0.0000106	2228
Missense in Polyphen		27	67.463	0.40022		788
Synonymous	0.696	60	67.3	0.892	0.00000357	645
Loss of Function	2.58	8	20.7	0.387	0.00000118	221

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000906	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000564	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000792	0.0000791
Middle Eastern	0.0000564	0.0000544
South Asian	0.000102	0.0000980
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein- effector interaction.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Relaxin signaling pathway - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Retrograde endocannabinoid signaling - Homo sapiens (human);GABAergic synapse - Homo sapiens (human);Serotonergic synapse - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Glutamatergic synapse - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Circadian entrainment - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Morphine addiction - Homo sapiens (human);Alcoholism - Homo sapiens (human);Beta-agonist/Beta-blocker Pathway, Pharmacodynamics;Myometrial Relaxation and Contraction Pathways;Chemokine signaling pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Ras Signaling;Calcium Regulation in the Cardiac Cell;Signaling by GPCR;Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding;Signaling by WNT;Signal Transduction;Glucagon signaling in metabolic regulation;Thromboxane signalling through TP receptor;Metabolism of proteins;ADP signalling through P2Y purinoceptor 12;Chaperonin-mediated protein folding;Metabolism;G alpha (s) signalling events;Presynaptic function of Kainate receptors;Activation of kainate receptors upon glutamate binding;Adrenaline,noradrenaline inhibits insulin secretion;Transport of small molecules;Glucagon-like Peptide-1 (GLP1) regulates insulin secretion;Regulation of insulin secretion;Signal amplification;Neuronal System;Thrombin signalling through proteinase activated receptors (PARs);Glucagon-type ligand receptors;Class B/2 (Secretin family receptors);GPCR ligand binding;Platelet activation, signaling and aggregation;Ca2+ pathway;Beta-catenin independent WNT signaling;ADP signalling through P2Y purinoceptor 1;Hemostasis;Protein folding;G-protein activation;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;Opioid Signalling;G alpha (i) signalling events;G alpha (12/13) signalling events;G alpha (z) signalling events;Vasopressin regulates renal water homeostasis via Aquaporins;Aquaporin-mediated transport;G beta:gamma signalling through PLC beta;Prostacyclin signalling through prostacyclin receptor;Integration of energy metabolism;Platelet homeostasis;G alpha (q) signalling events;G beta:gamma signalling through PI3Kgamma;G-protein beta:gamma signalling;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.130

Intolerance Scores

• loftool: 0.614
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.4

Haploinsufficiency Scores

• pHI: 0.454
• hipred: Y
• hipred_score: 0.729
• ghis: 0.557

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.915

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gnb4

Gene ontology

• Biological process: protein folding;signal transduction;substantia nigra development
• Cellular component: lysosomal membrane;cytosol;myelin sheath;extracellular exosome
• Molecular function: protein-containing complex binding